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Press release:
Clinical Trials in Alzheimer’s Disease
5 November, 2010
Toulouse, France
Since 1991, only five drugs have been approved in the European Union and United States
for the symptomatic treatment of Alzheimer's disease (AD). Moreover, no drugs are
available that can alter the course of the disease, despite a significant investment of time
and money by governments, the pharmaceutical industry, private sponsors, and academia.
At the Clinical Trials for Alzheimer's Disease (CTAD) meeting in Toulouse on Thursday,
4 November, 2010, clinicians and researchers expressed disappointment about the
failures of several recent drug trials, but vowed to learn from these trials as they press
forward in designing interventions that will be effective in the earliest stages of the
disease.
The reasons why so many recent drug trials have failed remain obscure, according to
most speakers at the conference. Are the drugs themselves unable to halt the disease
process, or are they being given at the wrong doses or for an insufficient amount of time?
Or perhaps the disease is too far advanced in people who have received the drugs. Maybe
multiple drugs will need to be delivered in combinations as they are for other diseases
such as cancer and AIDS. Only with additional research will scientists be able to untangle
the complexity of the disease process and thus find effective ways to intervene.
One point of agreement is that the disease develops over decades and that by the time
symptoms appear, interventions are unlikely to be effective. This realization has resulted
in a rethinking of the diagnostic criteria for the disease. New criteria were proposed in
July, 2010 by three workgroups convened in the United States by the National Institute
on Aging and the Alzheimer’s Association. They suggested updating the criteria to better
reflect the full range of the disease from its earliest effects to its eventual impact on
mental and physical function. Three different phases were proposed: 1) a presymptomatic, or pre-clinical, phase occurring many years before symptoms become
evident; 2) a symptomatic phase characterized by problems in cognition and memory but
not severe enough to limit the ability to live independently or carry out everyday
activities; and 3) Alzheimer's dementia, when the disease has progressed to the point that
the person has markedly impaired cognitive function and has lost the ability to function
independently.
Dr. Reisa Sperling, of Harvard Medical School, representing the pre-symptomatic
workgroup at CTAD, emphasized that this designation is meant for research purposes
only, not as a diagnostic category. Indeed, this is one of the most active areas of
Alzheimer's disease research, as scientists have been working to identify biological
markers of disease that would allow early identification and early treatment. For example,
researchers have developed a method for imaging deposits in the brain of a protein called
amyloid, which is considered a hallmark of Alzheimer's disease. These deposits are seen
in many elderly people who have no signs of cognitive impairment and are thought to be
predictive of incipient AD. If this indeed turns out to be an early “biomarker” of AD, it
could be used in the future to identify people who are candidates for early preventive
treatment. Other biochemical markers that can be measured in the cerebrospinal fluid are
also being studied to see if they are presymptomatic markers of the disease.
Biomarkers could transform the conduct of clinical trials according to many participants
at CTAD. By identifying people who are likely to develop AD in the future, they could
allow trials to enroll a smaller number of subjects; and they may also be useful in
tracking the effectiveness of a treatment, which could shorten the amount of time
required to demonstrate effectiveness. Both of these factors could dramatically increase
the efficiency of clinical trials.
“We now have tools now to test the idea of early treatment using biomarkers,” said Dr.
Paul Aisen from the University of California at San Diego. “So despite all the
discouraging news I am optimistic.”